Incremental Value of Cardiac Myosin-Binding Protein C for the Early Diagnosis of Acute Myocardial Infarction

Pedro Lopez-Ayala; Jasper Boeddinghaus; Luca Koechlin; Paolo Bima; Jonas Glaeser; Carlos C Spagnuolo; Luca Crisanti; Oscar Miro; Francisco Javier Martín-Sánchez; Michael Christ; Karin Wildi; Simona Piazza; Thomas Nestelberger; Maria Rubini Gimenez; Juliane Gehrke; Jude Formambuh; Emel Kaplan; Gabrielle Hure; Tobias Breidthardt; Evangelos Giannitsis; Bertil Lindahl; Michael Marber; Felix Mahfoud; Ivo Strebel; Christian Mueller; APACE and TRAPID-AMI investigators

doi:10.1016/j.jacc.2025.09.008

Incremental Value of Cardiac Myosin-Binding Protein C for the Early Diagnosis of Acute Myocardial Infarction

J Am Coll Cardiol. 2025 Oct 13:S0735-1097(25)07767-8. doi: 10.1016/j.jacc.2025.09.008. Online ahead of print.

Authors

Pedro Lopez-Ayala¹, Jasper Boeddinghaus¹, Luca Koechlin², Paolo Bima¹, Jonas Glaeser¹, Carlos C Spagnuolo¹, Luca Crisanti³, Oscar Miro⁴, Francisco Javier Martín-Sánchez⁵, Michael Christ⁶, Karin Wildi³, Simona Piazza³, Thomas Nestelberger¹, Maria Rubini Gimenez³, Juliane Gehrke³, Jude Formambuh³, Emel Kaplan³, Gabrielle Hure³, Tobias Breidthardt³, Evangelos Giannitsis⁷, Bertil Lindahl⁸, Michael Marber⁹, Felix Mahfoud³, Ivo Strebel¹⁰, Christian Mueller¹¹; APACE and TRAPID-AMI investigators

Collaborators

APACE and TRAPID-AMI investigators:
Desiree Wussler¹², Tobias Zimmermann¹², Dagmar I Keller¹³, Ksenija Slankamena¹³, Danielle M Gualandro¹², Andreas Buser¹⁴, Eliska Potlukova¹², Damian Kawecki¹⁵, Nicolas Geigy¹⁶, Katharina Rentsch¹⁷, Beata Morawiec¹⁵, Piotr Munzk¹⁵, Beatriz Lopez-Barbeito¹⁸, Gemma Martinez-Nadal¹⁸, Carolina Fuenzalida¹⁸, Sofia Calderón¹⁸, Esther Rodriguez Adrada¹⁹, Eva Ganovská²⁰, Jiri Parenica²⁰, Arnold von Eckardstein²¹, Isabel Campodarve²², Joachim Gea²², Roland Bingisser²³, Christian Nickel²³, James Mccord²⁴, Richard Nowak²⁵, Richard Body²⁶, Christopher R deFilippi²⁷, Robert H Christenson²⁸, Mauro Panteghini²⁹, Mario Plebani³⁰, Franck Verschuren³¹, John French³², Silvia Weiser³³, Tomas Jernberg³⁴, Aitor Alquézar-Arbé³⁵, Jordi Ordonez-Llanos³⁶, Tom Kaier³⁷

Affiliations

¹ Cardiovascular Research Institute Basel (CRIB) and Clinic of Cardiology, University Hospital Basel, Department of Clinical Research, University of Basel, Basel, Switzerland; GREAT network, Rome, Italy.
² Cardiovascular Research Institute Basel (CRIB) and Clinic of Cardiology, University Hospital Basel, Department of Clinical Research, University of Basel, Basel, Switzerland; GREAT network, Rome, Italy; Department of Cardiac Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.
³ Cardiovascular Research Institute Basel (CRIB) and Clinic of Cardiology, University Hospital Basel, Department of Clinical Research, University of Basel, Basel, Switzerland.
⁴ GREAT network, Rome, Italy; Emergency Department, Hospital Clinic, University of Barcelona, Barcelona, Spain.
⁵ GREAT network, Rome, Italy; Emergency Department, Hospital Clínico San Carlos, Madrid, Spain.
⁶ Department of Emergency Medicine, Luzerner Kantonsspital, Luzern, Switzerland.
⁷ Department of Medicine III, University Hospital Heidelberg, Heidelberg, Germany.
⁸ Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala, Sweden.
⁹ King's College London BHF Centre, Rayne Institute, St Thomas' Hospital, London, United Kingdom.
¹⁰ Cardiovascular Research Institute Basel (CRIB) and Clinic of Cardiology, University Hospital Basel, Department of Clinical Research, University of Basel, Basel, Switzerland; GREAT network, Rome, Italy. Electronic address: ivo.strebel@usb.ch.
¹¹ Cardiovascular Research Institute Basel (CRIB) and Clinic of Cardiology, University Hospital Basel, Department of Clinical Research, University of Basel, Basel, Switzerland; GREAT network, Rome, Italy. Electronic address: christian.mueller@usb.ch.
¹² Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Department of Clinical Research, University of Basel, Switzerland; GREAT network, Rome, Italy; (c)Department of Cardiology, Inselspital, University of Bern, Switzerland; (d)Emergency Department, Kantonsspital Luzern, Switzerland; (e)Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland.
¹³ Department of Cardiology, University Hospital Brno, Brno, Czech Republic and Medical Faculty, Masaryk University, Brno, Czech Republic.
¹⁴ Emergency Department, University Hospital Basel, Department of Clinical Research, University of Basel, Switzerland.
¹⁵ GREAT network, Rome, Italy; (c)Department of Cardiology, Inselspital, University of Bern, Switzerland; (d)Emergency Department, Kantonsspital Luzern, Switzerland; (e)Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland; 2nd Department of Cardiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Katowice, Poland.
¹⁶ Emergency Department, Kantonsspital Liestal, Switzerland.
¹⁷ Laboratory Medicine, University Hospital Basel, Switzerland.
¹⁸ GREAT network, Rome, Italy; (c)Department of Cardiology, Inselspital, University of Bern, Switzerland; (d)Emergency Department, Kantonsspital Luzern, Switzerland; (e)Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland; Emergency Department, Hospital Clinic, Barcelona, Catalonia, Spain.
¹⁹ GREAT network, Rome, Italy; (c)Department of Cardiology, Inselspital, University of Bern, Switzerland; (d)Emergency Department, Kantonsspital Luzern, Switzerland; (e)Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland; Emergency Department, Hospital Clínico San Carlos, Madrid, Spain.
²⁰ GREAT network, Rome, Italy; (c)Department of Cardiology, Inselspital, University of Bern, Switzerland; (d)Emergency Department, Kantonsspital Luzern, Switzerland; (e)Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland; Department of Cardiology, University Hospital Brno, Brno, Czech Republic and Medical Faculty, Masaryk University, Brno, Czech Republic.
²¹ Department of Laboratory Medicine, University Hospital Zurich, Zurich, Switzerland.
²² Hospital del Mar, Barcelona, Spain.
²³ GREAT network, Rome, Italy; (c)Department of Cardiology, Inselspital, University of Bern, Switzerland; (d)Emergency Department, Kantonsspital Luzern, Switzerland; (e)Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland; Emergency Department, University Hospital Basel, Department of Clinical Research, University of Basel, Switzerland.
²⁴ Heart and Vascular Institute, Henry Ford Health System, Detroit, Michigan, United States.
²⁵ Department of Emergency Medicine, Henry Ford Health System, Detroit, Michigan, United States.
²⁶ Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
²⁷ Inova Heart and Vascular Institute, Falls Church, Virginia, United States.
²⁸ University of Maryland School of Medicine, Baltimore, Maryland, United States.
²⁹ Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Milan Medical School, Milan, Italy.
³⁰ Department of Laboratory Medicine, University Hospital of Padova, Padua, Italy.
³¹ Department of Acute Medicine, Cliniques Universitaires St-Luc and Universite Catholique de Louvain, Brussels, Belgium.
³² Liverpool Hospital and University of New South Wales, Liverpool, NSW, Australia.
³³ Roche Diagnostics Germany, Penzberg, Germany.
³⁴ Department of Medicine, Karolinksa Institutet, Huddinge, Sweden.
³⁵ Emergency Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
³⁶ Department of clinical biochemistry, Universitat Autonoma, Barcelona, Spain.
³⁷ Cardiology Department Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK.

PMID: 41222525
DOI: 10.1016/j.jacc.2025.09.008

Abstract

Background: Cardiac myosin-binding protein C (cMyC) is a cardiac-specific sarcomeric protein with faster release kinetics compared with those of high-sensitivity cardiac troponin (hs-cTn).

Objectives: The aim of this study was to compare the diagnostic performance of cMyC, measured with a novel prototype automated immunoassay, with high-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity cardiac troponin I (hs-cTnI) for the early diagnosis of non-ST-segment elevation myocardial infarction (NSTEMI). Furthermore, we derived a single blood draw dual-biomarker strategy combining hs-cTn and cMyC and compared it with the hs-cTnT/I-only strategy endorsed by the European Society of Cardiology.

Methods: This was a secondary analysis from an international prospective study recruiting adult patients presenting to the emergency department (ED) with suspected NSTEMI. cMyC, hs-cTnT, and hs-cTnI concentrations were measured upon ED presentation. Final diagnoses were centrally adjudicated by 2 independent cardiologists blinded to cMyC values. To compare the single- and dual-biomarker strategy, safety (defined as the sensitivity and negative predictive value for ruling out index NSTEMI) and triage efficacy (defined as the proportion of patients triaged to either rule-out or rule-in) were assessed. The diagnostic endpoint was index NSTEMI. The prognostic endpoint was 30-day, 1-year, and 5-year cardiovascular death or MI. Findings were externally validated in an independent international cohort.

Results: Among 4,735 eligible patients, 854 (18%) were diagnosed with NSTEMI. The discrimination for NSTEMI at presentation was higher for cMyC (area under the curve [AUC]: 0.943; 95% CI: 0.936-0.95) than for hs-cTnT (AUC: 0.936; 95% CI: 0.929-0.944; P = 0.008). Differences were mainly driven by patients with chest pain onset ≤3 hours (AUC of 0.939 [95% CI: 0.928-0.951] vs 0.921 [95% CI: 0.907-0.936], respectively; P < 0.001). The dual-biomarker strategy increased overall triage efficacy from 26.8% (hs-cTnT only) to 60.0% (hs-cTnT and cMyC), without compromising safety during the index visit. Despite identifying up to 3 times more patients for rule-out, the dual-biomarker strategy showed comparable cumulative incidences of cardiovascular death or myocardial infarction at 30 days, 1 year, and 5 years. Similar results were observed with hs-cTnI and in the external validation cohort.

Conclusions: CMyC adds significant incremental value to hs-cTn values in the early diagnosis of NSTEMI, improving diagnostic discrimination and enabling more patients to be safely and immediately ruled out for NSTEMI. The single blood draw dual-biomarker strategy is particularly attractive in busy ED settings due to its simplicity and quick time-to-decision. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE]; NCT00470587).

Keywords: cMyC; myocardial infarction; troponin.

Associated data

ClinicalTrials.gov/NCT00470587